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Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability

Makoto Iimori (), Sugiko Watanabe, Shinichi Kiyonari, Kazuaki Matsuoka, Ryo Sakasai, Hiroshi Saeki, Eiji Oki, Hiroyuki Kitao and Yoshihiko Maehara
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Makoto Iimori: Graduate School of Medical Sciences, Kyushu University
Sugiko Watanabe: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University
Shinichi Kiyonari: Nagoya University Graduate School of Medicine
Kazuaki Matsuoka: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University
Ryo Sakasai: Kanazawa Medical University
Hiroshi Saeki: Graduate School of Medical Sciences, Kyushu University
Eiji Oki: Graduate School of Medical Sciences, Kyushu University
Hiroyuki Kitao: Graduate School of Medical Sciences, Kyushu University
Yoshihiko Maehara: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Temporal regulation of microtubule dynamics is essential for proper progression of mitosis and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Here we show that Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. We propose that Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, thereby ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11117

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DOI: 10.1038/ncomms11117

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